Evaluation of left ventricular function is of interest for both diagnostic and therapeutic applications. During normal cardiac function the cardiac chambers observe consistent time-dependent relationships during the systolic (contractile) phase and the diastolic (relaxation) phase of the cardiac cycle. During cardiac dysfunction associated with pathological conditions or following cardiac-related surgical procedures, these time-dependent mechanical relationships are often altered. This alteration, when combined with the effects of weakened cardiac muscles, reduces the ability of the ventricle to generate contractile strength resulting in hemodynamic insufficiency.
Ventricular dyssynchrony following coronary artery bypass graft (CABG) surgery is a problem encountered relatively often, requiring post-operative temporary pacing. Atrio-biventricular pacing has been found to improve post-operative hemodynamics following such procedures. See Weisse et al., Thorac. Cardiovasc. Surg. 2002;41:131-135. A widely accepted, standardized method for selecting pacing sites and pacing intervals that provide the greatest hemodynamic benefit to the patient during the critical recovery phase, however, has not been available.
Chronic ventricular resynchronization therapy has been clinically demonstrated to improve indices of cardiac function in patients suffering from congestive heart failure. Cardiac pacing may be applied to one or both ventricles or multiple heart chambers, including one or both atria, to improve cardiac chamber coordination, which in turn is thought to improve stroke volume and pumping efficiency. Clinical follow-up of patients undergoing resynchronization therapy has shown improvements in hemodynamic measures of cardiac function, left ventricular volumes, and wall motion. See, for example, Gras D et al., Eur J Heart Fail. 2002;4:311-20; and Sogaard P et al., J Am Coll Cardiol. 2002;40:723-30. However, not all patients respond favorably to cardiac resynchronization therapy. Physicians are challenged in selecting patients that will benefit and in selecting the optimal pacing intervals between the atria and ventricles (A-V intervals) and between the ventricles (V-V intervals), collectively referred to herein as “A-V-V” intervals, applied to resynchronize the heart chamber contractions.
Selection of pacing intervals may be based on echocardiographic studies performed to determine the settings resulting in the best hemodynamic response. Significant hemodynamic changes may not always be acutely observable in an individual patient using non-invasive monitoring methods. Selection of parameters may therefore be based on avoidance of altered or impeded ventricular filling. In the MIRACLE clinical trial conducted to evaluate resynchronization therapy, the A-V-V intervals were optimized individually in patients by shortening the A-V interval to maximize LV filling without truncating the atrial contribution as observed by echocardiography and to maximize stroke volume. Acute increases in stroke volume have been related to chronically sustained clinical benefits. In fact, patients acutely optimized based on stroke volume have exhibited chronic improvements in sustained stroke volume measures.
Echocardiographic approaches for optimizing resynchronization therapy provide only an open-loop method for selecting pacing intervals. After evaluating the hemodynamic effect of varying combinations of pacing intervals, a clinician must manually select and program the desired parameters. Furthermore, an echocardiographic procedure for optimizing resynchronization therapy can require substantial time and personnel. A technician is required to program A-V-V timing schemes while a sonographer interprets the effects on the heart. A period of hemodynamic stabilization is generally desired prior to evaluating the hemodynamic effects of a particular timing scheme. However, the time required to reach hemodynamic stability may be uncertain.
A closed-loop method for selecting pacing intervals for resynchronization therapy that reduces the time and personnel required for testing various A-V-V timing schemes is therefore desirable. A closed-loop method preferably accounts for a period of hemodynamic stabilization and optimizes the A-V-V intervals such that the resultant effect on stroke volume is maximized. Furthermore, a closed-loop method that may be fully implemented in an implantable device would advantageously allow periodic re-optimization of A-V-V intervals in order to maintain an optimal hemodynamic benefit chronically.
Numerous algorithms for optimizing the A-V interval during dual chamber pacing to improve cardiac function or hemodynamic status have been described including automatic algorithms based on an implantable sensor of hemodynamic function. Measurements of impedance to assess cardiac output, intracardiac blood pressure sensors, acoustical sensors for monitoring heart sounds, a Doppler ultrasound sensor for monitoring flow have all been proposed for assessing cardiac function using an implantable device. Reference is made, for example, to U.S. Pat. No. 5,334,222 to Salo et al., and U.S. Pat. No. 6,477,406 issued to Turcott.
Multichamber pacing systems having automated selection of pacing intervals have also been proposed. A four-chamber pacing system that includes impedance sensing for determining the timing of right heart valve closure or right ventricular contraction and adjusting the timing of delivery of left ventricular pace pulses is generally disclosed in U.S. Pat. No. 6223,082 issued to Bakels, et al., incorporated herein by reference in its entirety. Programmable coupling intervals selected so as to provide optimal hemodynamic benefit to the patient in an implantable multichamber cardiac stimulation device are generally disclosed in U.S. Pat. No. 6,473,645 issued to Levine, incorporated herein by reference in its entirety. Improvement in cardiac function is based on a generic physiological sensor. Such automated systems have not been put to clinical use to date.
A need remains, therefore, for a practical method for automatically assessing the hemodynamic response to different A-V-V timing schemes during cardiac resynchronization therapy and identifying optimal A-V-V timing schemes, both acutely and chronically.